The long-term objectives of this research program are: to understand the processes which determine differential gene expression, and to assess the contribution of disturbed patterns of gene expression in the onset and maintenance of malignancy. These studies will focus on small stable RNA molecules which are found in the nucleus. The specific goal of these studies is to assign functions to small stable RNA (ss RNA) molecules. This objective will be pursued by a combination of physiological, biochemical and genetical analyses. In order to assess the function of the ssRNA molecules in the onset of malignancy, an attempt will be made to induce tumors chemically in the mouse liver and to follow the metabolism of ssRNA in the liver of these animals. The distribution of the genes corresponding to ssRNA in the mouse genome will be studied by nucleic acid hybridizations on gels. We shall determine whether ssRNA is more abundant in active or inactive chromatin, and to what extent it is part and parcel of chromatin. In order to assess whether the metabolism of ssRNA is affected in human tumors, fragments of tumors will be grafted to nude mice in which the metabolism of ssRNA will be studied.